Several processes for coating carriers with particles are known in the art. One typical process is performed by using a fluidized bed as the carrier. A fluidized bed is formed when a quantity of a solid particulate substance (usually present in a holding vessel) is placed under appropriate conditions to cause the solid/fluid mixture to behave as a fluid. This is usually achieved by the introduction of pressurized fluid through the particulate medium. This results in the medium then having many properties and characteristics of normal fluids.
According to one process known in the art, droplets of a suspension are sprayed on a fluidized bed, normally using a Wurster apparatus. The Wurster apparatus generally includes a container with a cylindrical partition extending upwardly therein, and with a perforated plate or screen at the lower end thereof to define a bottom wall for the particles. The partition is spaced above the perforated plate. The area within the cylindrical partition defines the upbed of the container, while the area outside the partition defines the downbed of the container. The perforated plate includes an area of large perforations and a greater percentage of perforated open area through which air flows into the upbed at an increased velocity, and an area of perforations with a lower percentage of open area through which air flows into the downbed at a decreased velocity. The higher velocity air in the upbed area transports the particles for coating, layering, and drying of a coating solution sprayed from a spray nozzle extending upwardly through the perforated plate and into the upbed area. The particles then encounter the lower velocity air in the expansion chamber above the partition. When the air velocity is insufficient to support the product, the particles fall into the downbed area for reentry into the higher velocity air, such that a cycle of coating in the upbed area and drying in the downbed area is achieved. Various forms of the Wurster apparatus and process are disclosed in U.S. Pat. Nos. 2,648,609, 2,799,241, 3,089,824, 3,196,827, 3,207,824, and 3,253,944.
In the pharmaceutical industry, an API (active pharmaceutical ingredient) is commonly introduced into the patient's body deposed on a carrier. Carriers are substances which are used to improve the performance of the dose form by increasing the uniformity of the blend and keep the API particles from aggregating. Many substances are known to be suitable as carriers in the pharmaceutical industry, for example: micro-crystalline cellulose, lactose and mannitol. Those skilled in the art generally choose a carrier based on its particle size distribution and solubility properties.
The Wurster apparatus method of coating results in carriers which are coated with a layer of API crystals with a large range of sizes. This layer is created due to the adherence of the droplets to the carrier particles prior to the evaporation of the solvent. In this method, the particles of API are suspended in a dispersion liquid. If the API particles are very small, they may aggregate and the suspension will not be uniform. In many cases, the API particles are not stable in the suspension, and the process should be performed soon after the creation of the suspension.
Furthermore, it may be readily understood that the Wurster apparatus method is not suitable for coating carrier particles with microdroplets of API solution or air-suspended dry microparticles because of the low probability of a microparticle or microdroplet to collide with a carrier particle. In this case, the microparticles might escape through the filtering system and the material will be lost.
Many efforts have been made to formulate suitable therapeutic agents as dry powders for delivery via inhalers. Typically, the formulations are produced by drying the active agent in the presence of certain excipients, such as polysaccharides or citrate, to enhance stability during the drying process or in storage.
CA-A-2136704 discloses a product obtained by spray-drying a medicinal substance such as insulin (among many others) and a carrier. WO-A-9735562 discloses spray-drying a solution of insulin and a polysaccharide. WO-A-9524183 is directed primarily to a dry powder that comprises insulin and a carrier material, typically a saccharide, in the form of an amorphous powder of microparticles obtained by spray-drying. WO95/23613 discloses a spray-dried DNase formulation. U.S. Pat. No. 6,926,908 discloses spray-dried therapeutic agent at high concentrations.
There is a need in the art for methods of coating carriers with microparticles of an API that are either suspended in air or formed from microdroplets.